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Article

Decreases in Sympathetic Activity Due to Low-Intensity Extremely Low-Frequency Electric Field Treatment Revealed by Measurement of Spontaneous Fluctuations in Skin Conductance in Healthy Subjects

1
Department of Psychiatry, Shizuoka Saiseikai General Hospital, 1-1-1, Oshika, Suruga-ku, Shizuoka 422-8527, Japan
2
Research Division, Saiseikai Research Institute of Health Care and Welfare, 26F Mita Kokusai Building, 1-4-28, Mita, Minato-ku, Tokyo 108-0073, Japan
3
Research and Development Department, Hakuju Institute for Health Science Co., Ltd., 1-37-5, Tomigaya, Shibuya-ku, Tokyo 151-0063, Japan
4
Bio-Self-Regulating Science Laboratory, Obihiro University of Agriculture and Veterinary Medicine, Inada-Cho, Obihiro 080-8555, Japan
*
Author to whom correspondence should be addressed.
Appl. Sci. 2024, 14(20), 9336; https://doi.org/10.3390/app14209336
Submission received: 12 September 2024 / Revised: 5 October 2024 / Accepted: 9 October 2024 / Published: 14 October 2024

Abstract

:

Featured Application

A low-intensity extremely low-frequency electric field treatment can be applied for stress management in healthcare by reducing sympathetic activity and promoting relaxation.

Abstract

(1) Background: Our previous studies indicated that low-intensity extremely low-frequency electric field (ELF-EF) treatment alters autonomic activities, as revealed through heart rate variability (HRV) analysis. However, the high-frequency (HF) component of HRV that reflects parasympathetic activity showed no changes either during or after the end of the treatment, suggesting the involvement of sympathetic nerves. (2) Methods: To examine this issue in the present study, the effect of ELF-EF on skin conductance (SC), which is controlled solely by sympathetic nerves, was analyzed. Twelve healthy subjects underwent a 20 min ELF-EF treatment (applied voltage: 9 kV, induced current density: below 6 mA/m2) and a sham treatment in a random order with an interval of more than 2 weeks. SC and HRV were recorded under the eyes-open condition during a 2 min period both before and after the treatment. (3) Results: The number of spontaneous fluctuations in skin conductance (SC-SFs) significantly decreased after the ELF-EF treatment, suggesting psychological changes, including relaxation. The skin conductance level, heart rate, and HRV indices did not change after the ELF-EF treatment. (4) Conclusion: The results support the idea that low-intensity ELF-EF affects autonomic nerves by reducing sympathetic activity, as reflected by SC-SFs.

1. Introduction

The biological effects of extremely low-frequency electric fields (ELF-EFs) have been extensively studied for their safe use in various conditions, and lowering the electric field intensity has been found to be effective in avoiding adverse influences, including brain and cardiac symptoms [1,2,3]. At the same time, beneficial changes in humans have also been reported. Low-intensity ELF-EF ameliorates pain due to rheumatoid arthritis [4] and chronic pain of undetermined origin [5]. Low-intensity ELF-EF generates physiological changes related to arousal reduction, leading to relaxation [6], which may underly its beneficial effects. In rodents, it is known that an ELF-EF reduces stress-related hormonal changes [7]. These observations suggest that, when used at a low intensity, an ELF-EF can have therapeutic effects on psychosomatic disturbances, but the mechanisms underlying the effects are not well understood. The beneficial and adverse effects can be related to different biological mechanisms depending on the intensity of the ELF-EF. In contrast to a high-intensity ELF-EF, a low-intensity ELF-EF may be able to modify psychosomatic activities within their functional ranges. And the autonomic nervous system is a candidate to be assessed because it controls various psychosomatic functions in humans.
Previous research reported that the heart rate (HR) and heart rate variability (HRV) indices are altered during the application of a low-intensity ELF-EF and suggested that autonomic activity may be involved in the generation of the beneficial changes [6]. However, among the HRV indices, the high-frequency (HF) component, which reflects parasympathetic nerve activity, is not affected during or after the treatment. HRV is a fluctuation in the inter-beat interval, resulting in several rhythms, including a breathing-dependent HF component, which is related to parasympathetic nerve activity, and a blood-pressure-dependent low-frequency (LF) component, which is related to both sympathetic and parasympathetic nerve activities [8,9]. HRV analysis itself is not fully capable of assessing sympathetic nerve activity [10,11].
Among various autonomic measures, skin conductance is accepted as a convenient tool for the evaluation of sympathetic nerve activity [12]. Skin conductance reflects sweating, which is solely controlled by the sympathetic nervous system [13,14]. Two types of skin conductance are measured: the skin conductance level (SCL) and skin conductance fluctuations (SCFs). The former represents the total sweating on the skin, and the latter is related to psychological status, including anxiety and tension [15]. SCFs are elicited by external stimuli (skin conductance response) or are generated spontaneously in the resting condition (spontaneous fluctuations in skin conductance; SC-SFs). The present study aimed to evaluate the effects of low-intensity ELF-EF on the sympathetic activity in the resting condition using two measures of skin conductance, SCL and SC-SF, in addition to the parasympathetic HRV index.

2. Materials and Methods

2.1. Ethical Background

This study was conducted in accordance with the principles of the Declaration of Helsinki. The experimental protocol was approved by the institutional review board of Shizuoka Saiseikai General Hospital (no. 2-14-02), and written informed consent to participate in the experiment was obtained from all subjects.
For the ELF-EF treatment, we used the device and parameters for EF generation for therapeutic use approved by the Ministry of Health, Labor, and Welfare of the Japanese Government.

2.2. Subjects and Experimental Protocol

Twelve healthy subjects (age: 62.2 ± 15.1 years, mean ± s.d., 10 females and 2 males) were voluntarily enrolled in this experiment, and underwent two treatment sessions: EF treatment and sham treatment. Those who had a history of cardiac, metabolic, neurological, or psychiatric disorders were excluded. After 5 min of adaptation, the subjects’ skin conductance, heart rate, and heart rate variability were measured for 2 min in a resting eyes-open state both before and after an EF or sham treatment while they were sitting on a chair in the treatment room of Healthtron Shizuoka Co. (Shizuoka, Japan) where the EF generator was situated. In the sham treatment, the subjects sat on the chair without EF exposure. The sessions with the EF and sham treatments were conducted with an interval of more than two weeks to lessen the possible persisting effects of the previous treatment, and the order was randomly assigned to the subjects when they were enrolled; the session including the EF treatment was first administered to 6 subjects and the session including the sham treatment was first administered to the other 6 subjects (Scheme 1). During the treatment, the subjects were instructed to read books to maintain an awake state. The room temperature was controlled at 23 degrees centigrade.

2.3. Electric Field Treatment

For the ELF-EF treatment, an EF generator was used (HEF-K9000, Hakuju Institute for Health Science, Tokyo, Japan; Figure 1). From the EF generator, a 60 Hz sinusoidal waveform with an electric potential of 9000 V root mean square amplitude was applied for 20 min to the lower electrode, which was attached to the chair under the feet (Lower Electrode, Figure 1). The height, width, and depth of the chair were 149, 62, and 23 cm, respectively. Polyvinyl chloride plates covered the lower electrode to avoid direct contact between it and the feet. The upper electrode above the head was covered with ABS resin (Upper Electrode, Figure 1) and served as the ground. These treatment settings were based on our previous study [6].
Current induction in the human body was simulated through dosimetry using a phantom exposed to the same EF. A hollow plastic manikin (P11 basic patient care simulator; 3B Scientific, Hamburg, Germany; height: 174 cm, weight: 14 kg) was used as the phantom. This dosimetry system was developed for the present series of studies, and the details were published in our previous report [6]. Figure 1 describes the EF intensity measured on the surface of the phantom and the simulated distribution of the current density induced on the horizontal plane inside the body. A finite difference method with high computational efficiency was used for the numerical analysis of the EF [16,17]. The data indicated that the simulated surface electric field reached 50 kV/m at the distal parts of the body, but the induced current density inside the body was simulated mostly below 6 mA/m2 (Figure 1), indicating that the ELF-EF in the present study was of low intensity [1,2,3].

2.4. Skin Conductance Measurement

Skin conductance (SC) was measured between the first and second fingers with silver/silver chloride electrodes that had a diameter of 8 mm and were filled with electroconductive gel; they were placed on the palmar side of the distal phalanges of the first and the second fingers of the right hand [18]. A constant voltage of 0.5 V was applied between the electrodes, and the generated current was converted into voltage at a sampling rate of 10 Hz (Model 2701SC Bioderm, UFI, Morro Bay, CA, USA). The DC skin conductance output of Bioderm was set to 50 mV/μS and was used to measure SCL (μS). For the AC skin conductance data, a low-cut filter of 0.16 Hz was applied, and its output was set to 5 V/μS to count the number of SC-SFs with an amplitude of more than 20 nS (/min) (Figure 2). The threshold was set at 20 nS based on the previous studies with consideration of the electrode size and the noise level [12,18]. The SC-SF amplitude was measured as the difference between the inflection points of the baseline and the positive peak.
Both SCL and SC-SFs reflect sweat generated by sweat glands, which are controlled by sympathetic activity [12]. It is known that SCL directly reflects the total amount of sweat produced as a result of various conditional changes in temperature, circulation, metabolism, and psychological state [13,14]. On the other hand, SCFs are profoundly related to psychological conditions, including anxiety and tension [15]. SCFs are a type of orienting response that is usually evoked in response to arousal or stressful events [19,20], and they are used to evaluate various psychiatric disorders [21,22,23]. SCFs may reflect the internal arousal level [24].

2.5. Heart Rate Variability Measurement

Heart rate (HR) and heart rate variability (HRV) were measured using a biological amplifier system (MWM12, GMS, Tokyo, Japan) with an electrocardiogram (ECG) electrode (Blue sensor P-00-S, Ambu A/S, Ballerup, Denmark) placed on the chest. The beat-to-beat interval was calculated by detecting the R peaks in ECG. Each beat-to-beat interval was converted into the instantaneous HR per minute (/min), and fluctuations in the beat-to-beat interval were analyzed using the maximum entropy method (MemCalc, GMS, Tokyo, Japan) to calculate the low-frequency (LF; 0.04–0.15 Hz) and high-frequency (HF; 0.15–0.4 Hz) components of the HRV [9]. A frequency domain analysis was employed because the relation of the calculated components to sympathetic and parasympathetic activities were well elucidated. The HF component reflected parasympathetic activity, which was influenced by respiratory movement [8]. The LF component was related to blood pressure control, and both sympathetic and parasympathetic activities were involved in its generation [10]. MemCalc was employed in the present study because it has been successfully used to analyze HRV with a duration as short as 30 s in the data [25], and it was found to be adequate for lessening the distress of the subjects during the measurement.

2.6. Statistical Analysis

To examine the effects of EFs on the parameters of SC, HR, and HRV, a two-way repeated-measure analysis of variance (ANOVA) was applied to check the measurement time (‘Time (before vs. after)’) and presence of EF treatment (‘EF (EF vs. sham)’) factors, as well as their interaction. When the effects of the factors were significant (α = 0.05), Tukey’s post hoc multiple-comparison test was performed (Prism 8, Version 8.4.3, GraphPad Software, San Diego, CA, USA). When the examined factors were statistically significant, Spearman’s correlation coefficients were also calculated to check the relation to other parameters.

3. Results

3.1. Skin Conductance

Figure 2 shows an example of the data for a subject before and after the EF treatment. For the SC-SF analysis, the number of fluctuations larger than 20 nS was counted (filled circle in Figure 2, Spontaneous Fluctuations). In the analysis of SCL, the mean amplitude during the measurement was calculated (Figure 2, Conductance Level).
Figure 3 presents a summary of the data on SC-SFs and SCLs in the 12 subjects. The number of SC-SFs (/min, mean ± s.d.) in the EF treatment session was 3.58 ± 4.12 before the EF treatment and 1.58 ± 2.19 after the EF treatment. That in the sham treatment was 3.75 ± 5.19 before the sham treatment and 6.50 ± 5.93 after the treatment. The two-way repeated-measure ANOVA showed no significance for the Time factor (before vs. after, F(1, 11) = 0.1718, p = 0.6865) or the EF factor (EF vs. sham, F(1, 11) = 2.449, p = 0.1459), but it revealed that the interaction between the Time factor and the EF factor was significant (F (1, 11) = 11.10, p = 0.0067). Tukey’s post hoc multiple-comparison test showed that the number of SC-SFs after the EF treatment was significantly lower than that before the EF treatment (95% CI = 0.1111 to 3.889, p = 0.0372), indicating that the number of SC-SFs was significantly reduced by the EF treatment.
The SCL (μS, mean ± s.d.) in the EF treatment session was 3.40 ± 1.69 before the EF treatment and 3.41 ± 2.06 after the EF treatment. In the sham treatment, it was 4.82 ± 3.47 before the sham treatment and 5.629 ± 3.601 after the treatment. The two-way repeated-measure ANOVA showed no significance for the Time factor (F(1, 11) = 0.7156, p = 0.4156) and the interaction of the Time and EF factors (F(1, 11) = 0.5292, p = 0.4821), but it revealed that the EF factor was significant (F(1, 11) = 9.605, p = 0.0101), indicating that the SCLs in the EF and sham sessions were different in the same subject.
The relation between SCFs and the SCL before and after the EF and sham treatments is presented in Figure 4. The Spearman correlation coefficient was significant before (r = 0.7887, p = 0.0034) and after (r = 0.6694, p = 0.0211) the EF treatment, as well as before the sham treatment (r = 0.8116, p = 0.0024). No correlation was found after the sham treatment (r = 0.4378, p = 0.1555). When the SCL was high, the number of SCFs was large. The number of SCFs was positively correlated with the SCL before the EF and sham treatments and was maintained after the EF treatment. In the sham treatment session, a correlation was not observed after the treatment.

3.2. Heart Rate

The HR before and after the EF and sham treatments is presented in Figure 5. The HR (/min, mean ± s.d.) in the EF treatment session was 74.51 ± 9.65 before the EF treatment and 70.85 ± 8.51 after the EF treatment. In the sham treatment, it was 76.42 ± 10.42 before the sham treatment and 73.76 ± 10.50 after the treatment. The two-way repeated-measure ANOVA showed that the Time factor was significant (before vs. after, F(1, 11) = 10.33, p = 0.0082). The EF factor (EF vs. sham, F(1, 11) = 1.469, p = 0.2509) and the Time and EF interaction (F(1, 11) = 0.1550, p = 0.7013) were not significant. It was found that the HR was reduced after the treatment in both the EF and sham sessions.
The relationship between the skin conductance indices (SC-SFs and SCL) and HR is presented in Figure 6. In the EF treatment session, the Spearman correlation coefficients showed no correlations between the SC-SFs and HR both before (r = 0.4654, p = 0.1289) and after (r = 0.3222, p = 0.3021) the treatment. In the sham treatment session, the relationship was not significant before the treatment (r = 0.4440, p = 0.1489), but it was significant after the treatment (r = 0.6270, p = 0.0327). In the analysis of the SCL (Figure 6), no correlation was found in any of the conditions: before (r = 0.5035, p = 0.0989) or after (r = 0.07005, p = 0.8294) the EF treatment and before (r = 0.3636, p = 0.2464) or after (r = 0.5245, p = 0.0839) the sham treatment.

3.3. Heart Rate Variability

The HRV indices (LF, HF, and LF/HF) before and after the EF and sham treatments are presented in Table 1. For the LF component, the two-way repeated-measure ANOVA indicated that there were no significant effects of the Time factor (before vs. after), the EF factor, or their interaction (F(1, 11) = 1.970, p = 0.1881; F(1, 11) = 0.5987, p = 0.4554; F(1, 11) = 0.8219, p = 0.3841, respectively). For the HF component, no significant effects of the Time factor (before vs. after), the EF factor, or their interaction were found (F(1, 11) = 0.5172, p = 0.4870; F(1, 11) = 0.2256, p = 0.6441; F(1, 11) = 3.299, p = 0.0966, respectively). For LF/HF, no significant effects of the Time factor (before vs. after), the EF factor, or their interaction were found (F(1, 11) = 3.503, p = 0.0881; F(1, 11) = 0.003398; p = 0.9546; F(1, 11) = 3.680, p = 0.0814, respectively). No significant changes in the HRV indices were observed after the EF treatment in the present study.
The correlation between the HRV indices (LF, HF, LF/HF) and SC indices (SC-SFs, SCL) was assessed before and after the EF and sham treatments. The Spearman correlation coefficients indicated no statistically significant correlations between these indices (p > 0.05).

4. Discussion

4.1. Effects of the ELF-EF on SC

In the present study, the effects of a 9000 V ELF-EF treatment on the number of SC-SFs were observed, which was significantly reduced after 20 min of treatment. The simulated induced current was low (below 6 mA/m2), and it was revealed that a low-intensity ELF-EF can modulate autonomic activity, as reflected by SC-SFs. The SCL, on the other hand, was not altered by the ELF-EF treatment (Figure 3). SC represents sweating with multifunctional significance, as described in the Methods Section. Among the SC indices, the SCL measures the absolute level of conductance due to the presence of sodium chloride ions in the skin and reflects the total amount of sweat. In the present study, the total amount of sweating was not affected by the ELF-EF treatment. Sweating is affected by various indices, including temperature, metabolism, circulation, and psychological status, leading to changes in the SCL [12,13,14]. It was assumed that the low-intensity ELF-EF used in the present study did not modify the sweat gland activity as a whole.
SC-SFs are intimately related to psychological status, including anxiety and tension [15]. The changes in SC-SFs in the present study may have been evaluated as a reduction in anxiety and tension, which can be a basis for the use of low-intensity ELF-EF treatment applied for stress management in healthcare by reducing sympathetic activity and promoting relaxation.
SC-SFs are a type of skin conductance response without obvious external triggering stimuli. The response of skin conductance to external stimuli, such as tones, has been utilized to analyze arousal, attention, and habituation in various mental disorders, including schizophrenia [24]. Central noradrenergic activity is involved in controlling the skin conductance response through the sympathetic pathway [24]. Noradrenergic neuronal activity is known to be related to changes in the arousal level [26]. The present results for SC-SFs may have been generated by the effects of the ELF-EF on noradrenergic activity. Future studies with catecholamine measurement are necessary to assess this possibility.
In the present study, the SCL in the sham session was greater than that in the treatment session both before and after the treatment (Figure 3). The SCL can be affected by various factors, including temperature, metabolism, and circulation [12,13,14]; the difference in the SCL found between the EF and sham sessions may be explained by these conditions on the experimental days. It is suggested that the SCL itself is influenced by various conditions other than psychological factors.
The present study also showed that the number of SC-SFs and the SCL were significantly correlated both before and after the EF treatment (Figure 4). Since a correlation was not observed after the sham treatment, the persistence of the correlation between SCFs and the SCL may have been a result of the effects of the ELF-EF treatment. A study with a larger sample size will be necessary to assess this issue. After the EF treatment, the number of SCFs was reduced without changes in the SCL, and the correlation between these two parameters persisted. This phenomenon can be explained by the effects of the EF treatment on sweating mainly being related to psychological status but not to the control of temperature and metabolism. The measurement of both the SCL and SC-SFs can reveal multiple aspects of the function of sweat.

4.2. Effects of the ELF-EF on HR

The present study showed that the HR significantly decreased after the treatment in both the EF and sham sessions (Figure 5), indicating that the decrease was not an effect of the EF treatment. Before the start of the session, 5 min of adaptation was introduced for both the EF and sham treatments. The following 20 min in the sitting position could have decreased the sympathetic activity and increased the parasympathetic activity, but the SC and HRV did not present this change in sympathetic/parasympathetic balance. HR can be useful in totally evaluating the autonomic balance.

4.3. Effects of the ELF-EF on HRV Indices

In the present study, the HRV indices (LF, HF, and LF/HF) were not altered by the EF treatment (Table 1). These results are in accordance with our previous studies using a 30 kV ELF-EF [6]. The HF score, which reflected parasympathetic activity, did not change with the decrease in the number of SC-SFs, suggesting that the sympathetic activity was mainly modulated by the present low-intensity ELF-EF. In our previous study [6], the LF component was elevated during the ELF-EF treatment, but the change did not persist after the end of the treatment. It was suggested that the autonomic effects of EF reflected in the HRV indices could be transient. The main effects of the ELF-EF would be on the sympathetic activity.
The relationship between the HRV and SC indices was assessed, but the results were all negative, including those from before the treatment. In the present low-intensity ELF-EF treatment, the relation between HRV and SC was also not altered. The LF and LF/HF indices have been used to evaluate sympathetic activity in previous studies [9], but they showed no relationship with SC-SFs and SCL, which reflect sympathetic activity. The use of HRV indices to assess sympathetic activity would be misleading [10,11].

4.4. Mechanisms of the Effects of the ELF-EF on Sympathetic Activity

The mechanisms of the effect of the ELF-EF on sympathetic activity cannot be clarified from the present data. Possible candidate mechanisms are presented in the following.
It can be assumed that the EF acted on the skin surface to directly modify the distal part of the sympathetic nerve connecting to the sweat glands to produce a reduction in SC-SFs. The skin is known to generate an endogenous electric field with an intensity of several volts/m [27], and this is related to sweat production. In the present study, the exogenous ELF-EF may have affected the skin’s potential to modify the SC-SFs. However, the lack of changes in the SCL found in the present study was not explained by the direct effects of the EF on the skin. The relation of SCFs to orienting and arousing responses that are possibly generated in the central nervous system would also not comply with the peripheral mechanisms of EFs.
The skin changes induced by EFs may also be transmitted to the central autonomic area to produce a reduction in sympathetic activity. The vibration of skin and skin hair is known to generate changes in skin circulation, which can be detected by the central nervous system to alter autonomic activities [28].
The EF may directly act on the central nervous system and generate autonomic changes. It has been reported that ELF-EFs generate alterations in EEG, which is an endogenous EF clinically used for the evaluation of brain activity [29]. Theta and alpha waves increase their power during EF treatment, suggesting the lowering of arousal levels [6]. The arousal level is intimately related to autonomic control [30]. Lowered arousal levels may be related to reductions in SC-SFs. The mechanisms of changes in EEG due to ELF-EFs have not yet been clarified. Hormonal changes induced by ELF-EFs may mediate these changes [7]. Ephaptic modulation of the nervous system by ELF-EFs may also be a candidate mechanism [31]. Future research is necessary to validate these possibilities.

4.5. Limitation

In the present study, only one intensity of electric field was employed. EF treatments with other intensities may produce different effects on autonomic activity. A treatment length of longer than 20 min can also induce different results. In addition, the number of subjects was small in the present study (n = 12). A larger sample size may reveal additional aspects of the effects of EFs on autonomic indices, as well as the relationships between autonomic indices. Ten of twelve subjects in the present study were female, and the mean age was 62.2 years. The gender and age distribution should also be balanced in future studies. Future studies with other EF intensities and different durations in a larger sample would be important for the utilization of ELF-EFs in the field of healthcare.
The food content, amount of water intake, body weight, lifestyle, stress level, and sleep/awake schedule could also affect SC and HRV, but were not examined in the present small samples. Future studies are necessary to control these factors.
The time course of the effects of EFs after the end of EF treatment should also be clarified in future studies. The present study only assessed the changes immediately after the end of the treatment. The persistence of the effects of EFs can lead to the clinical application of ELF-EFs.
The present study did not examine the changes in subjective sensations following the EF treatment. Decreases in sympathetic activity can modify psychosomatic symptoms such as pain and fatigue. It is important to assess this issue in future research.

5. Conclusions

The number of spontaneous fluctuations in skin conductance (SC-SFs) decreased after the low-intensity ELF-EF treatment. The skin conductance level, heart rate, and heart rate variability indices showed no change. Low-intensity ELF-EF treatment affects autonomic nerves by reducing sympathetic activity, as reflected by SC-SFs, and may be applied for stress management in healthcare by promoting relaxation

Author Contributions

Conceptualization, T.S. and T.N.; methodology, T.S.; software, T.S.; validation, T.S., T.N. and S.H.; formal analysis, T.S.; investigation, T.S.; resources, T.N.; data curation, T.S.; writing—original draft preparation, T.S.; writing—review and editing, T.S.; supervision, S.H. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

The experimental protocol in this study was approved by the institutional review board of Shizuoka Saiseikai General Hospital (approval number: 2-14-02, approval date: 13 November 2020).

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon request. The data are not publicly available due to privacy and ethical restrictions.

Acknowledgments

The authors sincerely thank the members of Healthtron Shizuoka Co. for their cooperation in this study.

Conflicts of Interest

Authors Takaki Nedachi and Shinji Harakawa were employed by the company Hakuju Institute for Health Science Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

  1. International Commission on Non-Ionizing Radiation Protection. Guidelines for limiting exposure to time-varying electric and magnetic fields (1 Hz to 100 kHz). Health Phys. 2010, 99, 818–836. [Google Scholar] [CrossRef] [PubMed]
  2. International Commission on Non-Ionizing Radiation Protection. Guidelines for limiting exposure to time-varying electric, magnetic, and electromagnetic fields (up to 300 GHz). International commission on nonionizing radiation protection. Health Phys. 1998, 74, 494–522. [Google Scholar]
  3. World Health Organization. Extremely Low Frequency Fields Environmental Health Criteria Monograph No. 238. 2007. Available online: https://www.who.int/publications/i/item/9789241572385 (accessed on 11 September 2024).
  4. Naito, Y.; Yamaguchi, S.; Mori, Y.; Nakajima, K.; Hashimoto, S.; Tomaru, M.; Satoh, Y.; Hitomi, Y.; Karita, M.; Hiwatashi, T.; et al. A randomized, double-blind, sham-controlled study of static electric field therapy by high voltage alternating current for active rheumatoid arthritis. J. Clin. Biochem. Nutr. 2013, 53, 63–67. [Google Scholar] [CrossRef]
  5. Shinba, T.; Takahashi, K.; Kanetaka, S.; Nedachi, T.; Yamaneki, M.; Doge, F.; Hori, T.; Harakawa, S.; Miki, M.; Hara, H.; et al. A pilot study on electric field therapy for chronic pain with no obvious underlying diseases. Jpn. J. Integr. Med. 2012, 5, 68–72. [Google Scholar]
  6. Shinba, T.; Nedachi, T.; Harakawa, S. Alterations in heart rate variability and electroencephalogram during 20-minute extremely low frequency electric field treatment in healthy men during the eyes-open condition. IEEJ Trans. Electr. Electron Eng. 2023, 18, 38–44. [Google Scholar] [CrossRef]
  7. Harakawa, S.; Takahashi, I.; Doge, F.; Martin, D.E. Effect of a 50 Hz electric field on plasma ACTH, glucose, lactate, and pyruvate levels in stressed rats. Bioelectromagnetics 2004, 25, 346–351. [Google Scholar] [CrossRef] [PubMed]
  8. Akselrod, S.; Gordon, D.; Madwed, J.B.; Snidman, N.C.; Shannon, D.C.; Cohen, R.J. Hemodynamic regulation: Investigation by spectral analysis. Am. J. Physiol. 1985, 249, H867–H887. [Google Scholar] [CrossRef] [PubMed]
  9. Malik, M. Heart rate variability: Standards of measurement, physiological interpretation, and clinical use. Circulation 1996, 93, 1043–1065. [Google Scholar] [CrossRef]
  10. Goldstein, D.S.; Bentho, O.; Park, M.Y.; Sharabi, Y. Low frequency power of heart rate variability is not a measure of cardiac sympathetic tone but may be a measure of modulation of cardiac autonomic outflows by baroreflexes. Exp. Physiol. 2011, 96, 1255–1261. [Google Scholar] [CrossRef]
  11. Huang, W.L.; Ko, L.C.; Liao, S.C. The association between heart rate variability and skin conductance: A correlation analysis in healthy individuals and patients with somatic symptom disorder comorbid with depression and anxiety. J. Integr. Med. Res. 2022, 50, 3000605221127104. [Google Scholar] [CrossRef]
  12. Siddle, D.A.; Turpin, G.; Spinks, J.A.; Stephenson, D. Peripheral measures. In Handbook of Biological Psychiatry: Part II Brain Mechanisms and Abnormal Behavior-Psychophysiology; van Praag, H.M., Lader, M.H., Rafaelsen, O.J., Sachar, E.J., Eds.; Marcel Dekker Inc.: New York, NY, USA, 1980; pp. 45–78. [Google Scholar]
  13. Nicholls, J.; Martin, A.R.; Wallace, B.G.; Fuchs, P.A. From Neuron to Brain, 4th ed.; Sinauer Associates Inc.: Sunderland, MA, USA, 2021; pp. 315–332. [Google Scholar]
  14. Low, P.A. The sweat gland. In Primer on the Autonomic Nervous System, 2nd ed.; Robertson, D., Biaggioni, I., Burnstock, G., Low, P.A., Eds.; Elsevier Academic Press: San Diego, CA, USA, 2004; pp. 124–126. [Google Scholar]
  15. Lader, M.H. The psychophysiology of anxiety. In Handbook of Biological Psychiatry: Part II Brain Mechanisms and Abnormal Behavior-Psychophysiology; van Praag, H.M., Lader, M.H., Rafaelsen, O.J., Sachar, E.J., Eds.; Marcel Dekker Inc.: New York, NY, USA, 1980; pp. 225–247. [Google Scholar]
  16. Nakata, I.; Shimooka, T.; Shimizu, K. Analysis of human exposure of ELF electric field. Tech. Rep. IEICE EMCJ. 1998, 97–106, 47–54. [Google Scholar]
  17. Doge, F. Application software for electric field calculation with useful GUI. In Proceedings of the Symposium on 20th Biological and Physiological Engineering, Tokyo, Japan, 13–16 November 2005; pp. 123–126. [Google Scholar]
  18. Hasebe, H.; Shinba, T. Decreased anxiety after catheter ablation for paroxysmal atrial fibrillation is associated with augmented parasympathetic reactivity to stress. Heart Rhythm O2 2020, 1, 189–199. [Google Scholar] [CrossRef] [PubMed]
  19. Liu, J.C.; Verhulst, S.; Massar, S.A.; Chee, M.W. Sleep deprived and sweating it out: The effects of total sleep deprivation on skin conductance reactivity to psychosocial stress. Sleep 2015, 38, 155–159. [Google Scholar] [CrossRef] [PubMed]
  20. Gunther, A.C.; Bottai, M.; Schandl, A.R.; Storm, H.; Rossi, P.; Sackey, P. Palmar skin conductance variability and the relation to stimulation, pain and the motor activity assessment scale in intensive care unit patients. Crit. Care 2013, 17, R51. [Google Scholar] [CrossRef] [PubMed]
  21. Gruzelier, J.; Venables, P. Bimodality and lateral asymmetry of skin conductance orienting activity in schizophrenics: Replication and evidence of lateral asymmetry in patients with depression and disorders of personality. Biol. Psychiatry 1974, 8, 55–73. [Google Scholar]
  22. Lemaire, M.; El-Hage, W.; Frangou, S. Increased affective reactivity to neutral stimuli and decreased maintenance of affective responses in bipolar disorder. Eur. Psychiatry 2015, 30, 852–860. [Google Scholar] [CrossRef]
  23. Gruber, J.; Hay, A.C.; Gross, J.J. Rethinking emotion: Cognitive reappraisal is an effective positive and negative emotion regulation strategy in bipolar disorder. Emotion 2014, 14, 388–396. [Google Scholar] [CrossRef]
  24. Yamamoto, K.; Shinba, T.; Yoshii, M. Psychiatric symptoms of noradrenergic dysfunction: A pathophysiological view. Psychiat. Clin. Neurosci. 2014, 68, 1–20. [Google Scholar] [CrossRef]
  25. Sawada, Y.; Ohtomo, N.; Tanaka, Y.; Tanaka, G.; Yamakoshi, K.; Terachi, S.; Shimamoto, K.; Nakagawa, M.; Satoh, S.; Kuroda, S.; et al. New technique for time series analysis combining the maximum entropy method and non-linear least squares method: Its value in heart rate variability analysis. Med. Biol. Eng. Comput. 1997, 35, 318–322. [Google Scholar] [CrossRef]
  26. Sara, S.J.; Bouret, S. Orienting and reorienting: The locus coeruleus mediates cognition through arousal. Neuron. 2012, 76, 130–141. [Google Scholar] [CrossRef]
  27. Li, Y.; He, J.; Fu, C.; Jiang, K.; Cao, J.; Wei, B.; Wang, X.; Luo, J.; Xu, W.; Zhu, J. Children’s pain identification based on skin potential signal. Sensors 2023, 23, 6815. [Google Scholar] [CrossRef] [PubMed]
  28. Shimizu, K.; Endo, H.; Matsumoto, G. Fundamental study on measurement of ELF electric field at biological body surfaces. IEEE Trans. Instrum. Meas. 1989, 38, 779–784. [Google Scholar] [CrossRef]
  29. Niedermeyer, E. Epileptic Seizure Disorders. In Electroencephalography: Basic Principles. Clinical Applications, and Related Fields, 5th ed.; Niedermeyer, E., Lopes Da Sylva, F., Eds.; Lippincott Williams and Wilkins: Philadelphia, PA, USA, 2005; pp. 505–619. [Google Scholar]
  30. Savić, B.; Murphy, D.; Japundžić-Žigon, N. The Paraventricular Nucleus of the Hypothalamus in Control of Blood Pressure and Blood Pressure Variability. Front. Physiol. 2022, 13, 858941. [Google Scholar] [CrossRef] [PubMed]
  31. Shinba, T. Functional Perspectives of Endogenous Electric Fields in Humans and Rodents: A Viewpoint on Ephaptic Physiology. In Fundamentals and Modern Applications; IntechOpen: London, UK, 2024. [Google Scholar] [CrossRef]
Scheme 1. Experimental protocol.
Scheme 1. Experimental protocol.
Applsci 14 09336 sch001
Figure 1. Electric field treatment system, simulated surface electric field (kV/m), and induced current density (mA/m2). The simulation was based on data obtained through dosimetry using a manikin. A detailed description can be found in the text.
Figure 1. Electric field treatment system, simulated surface electric field (kV/m), and induced current density (mA/m2). The simulation was based on data obtained through dosimetry using a manikin. A detailed description can be found in the text.
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Figure 2. Left: Electrodes for skin conductance measurement. Right: A set of recordings of the skin conductance fluctuations and conductance level in a subject before and after the electric field (EF) treatment. The peaks in the spontaneous fluctuations are indicated with a filled circle, and the amplitude was measured between the inflection points of the baseline and the positive peak.
Figure 2. Left: Electrodes for skin conductance measurement. Right: A set of recordings of the skin conductance fluctuations and conductance level in a subject before and after the electric field (EF) treatment. The peaks in the spontaneous fluctuations are indicated with a filled circle, and the amplitude was measured between the inflection points of the baseline and the positive peak.
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Figure 3. Spontaneous fluctuations in skin conductance and conductance levels before (filled column) and after (open column) the EF or sham treatment. The means and standard deviations (vertical bar) for the 12 subjects are presented. For spontaneous fluctuation, two-way repeated-measure ANOVA showed that the interaction of the Time (before vs. after) and EF factors (EF vs. sham) was significant. Tukey’s post hoc test indicated that the number of spontaneous fluctuations in skin conductance was lowered after the EF treatment (an asterisk). For conductance level, the EF factor was significant, indicating that the conductance level in the sham session was greater than that in the EF session both before and after the treatment.
Figure 3. Spontaneous fluctuations in skin conductance and conductance levels before (filled column) and after (open column) the EF or sham treatment. The means and standard deviations (vertical bar) for the 12 subjects are presented. For spontaneous fluctuation, two-way repeated-measure ANOVA showed that the interaction of the Time (before vs. after) and EF factors (EF vs. sham) was significant. Tukey’s post hoc test indicated that the number of spontaneous fluctuations in skin conductance was lowered after the EF treatment (an asterisk). For conductance level, the EF factor was significant, indicating that the conductance level in the sham session was greater than that in the EF session both before and after the treatment.
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Figure 4. Correlation between spontaneous fluctuations and the skin conductance level. Correlations were significant in the data before (r = 0.7887, p = 0.0034) and after (r = 0.6694, p = 0.0211) the EF treatment, as well as in the data before (r = 0.8116, p = 0.0024) the sham treatment (Spearman correlation coefficient). Filled circles indicate the individual data. Linear regression lines are presented to indicate data that showed statistical significance.
Figure 4. Correlation between spontaneous fluctuations and the skin conductance level. Correlations were significant in the data before (r = 0.7887, p = 0.0034) and after (r = 0.6694, p = 0.0211) the EF treatment, as well as in the data before (r = 0.8116, p = 0.0024) the sham treatment (Spearman correlation coefficient). Filled circles indicate the individual data. Linear regression lines are presented to indicate data that showed statistical significance.
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Figure 5. Heart rate before (filled column) and after (open column) the EF or sham treatments. The means and standard deviations (vertical bar) for the 12 subjects are presented. Two-way repeated-measure ANOVA indicated the effect of the Time factor (before vs. after, an asterisk). No significant effects of the EF factor (EF vs. sham) or the interaction of the Time and EF factors were observed.
Figure 5. Heart rate before (filled column) and after (open column) the EF or sham treatments. The means and standard deviations (vertical bar) for the 12 subjects are presented. Two-way repeated-measure ANOVA indicated the effect of the Time factor (before vs. after, an asterisk). No significant effects of the EF factor (EF vs. sham) or the interaction of the Time and EF factors were observed.
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Figure 6. Relationship of the heart rate with skin conductance spontaneous fluctuation (A) and with the skin conductance level (B) before and after the EF and sham treatments. Filled circles indicate individual data. Linear regression lines are presented in this Figure to show data with statistical significance.
Figure 6. Relationship of the heart rate with skin conductance spontaneous fluctuation (A) and with the skin conductance level (B) before and after the EF and sham treatments. Filled circles indicate individual data. Linear regression lines are presented in this Figure to show data with statistical significance.
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Table 1. Heart rate variability indices before and after the EF and sham treatments.
Table 1. Heart rate variability indices before and after the EF and sham treatments.
EFSham
Before TreatmentAfter TreatmentBefore TreatmentAfter Treatment
Means.d.Means.d.Means.d.Means.d.
LFms291.491.9186.9263.094.672.6138.0226.0
HFms2244.3158.0219.8182.0175.8142.4232.2213.4
LF/HF 0.420.301.121.250.730.410.790.67
EF: Electric field treatment; sham: no electric field; s.d.: standard deviation.
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MDPI and ACS Style

Shinba, T.; Nedachi, T.; Harakawa, S. Decreases in Sympathetic Activity Due to Low-Intensity Extremely Low-Frequency Electric Field Treatment Revealed by Measurement of Spontaneous Fluctuations in Skin Conductance in Healthy Subjects. Appl. Sci. 2024, 14, 9336. https://doi.org/10.3390/app14209336

AMA Style

Shinba T, Nedachi T, Harakawa S. Decreases in Sympathetic Activity Due to Low-Intensity Extremely Low-Frequency Electric Field Treatment Revealed by Measurement of Spontaneous Fluctuations in Skin Conductance in Healthy Subjects. Applied Sciences. 2024; 14(20):9336. https://doi.org/10.3390/app14209336

Chicago/Turabian Style

Shinba, Toshikazu, Takaki Nedachi, and Shinji Harakawa. 2024. "Decreases in Sympathetic Activity Due to Low-Intensity Extremely Low-Frequency Electric Field Treatment Revealed by Measurement of Spontaneous Fluctuations in Skin Conductance in Healthy Subjects" Applied Sciences 14, no. 20: 9336. https://doi.org/10.3390/app14209336

APA Style

Shinba, T., Nedachi, T., & Harakawa, S. (2024). Decreases in Sympathetic Activity Due to Low-Intensity Extremely Low-Frequency Electric Field Treatment Revealed by Measurement of Spontaneous Fluctuations in Skin Conductance in Healthy Subjects. Applied Sciences, 14(20), 9336. https://doi.org/10.3390/app14209336

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